Docket Number: EPA-HQ-OPP-2011-0448 

www.regulations.gov 

Fipronil Summary Document 

Registration Review: Initial Docket 

June 2011 

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TABLE OF CONTENTS 

 Page 

I. Preliminary Work Plan (PWP) 4 

II. Fact Sheet 12 

III. Summary of Data Gaps 19 

________________________________________ 

Please Note 

This Preliminary Work Plan and Fact Sheet summarize the Environmental Protection 

Agency's current position based on the following documents: 

1. Registration Review– Preliminary Problem Formulation for Ecological Risk and 

Environmental Fate, Endangered Species and Drinking Water Assessments for Fipronil, 

May 4, 2011. 

2. Fipronil. Human Health Assessment Scoping Document in Support of Registration 

Review, May 24, 2011. 

3. Fipronil: Review of Human Incidents. March 01, 2011. 

4. Screening Level Usage Analysis (SLUA) for Fipronil, August 24, 2010. 

5. BEAD Chemical Profile for Registration Review: Fipronil. May 25, 2011. 

6. Appendix A: Food/Feed & Non-Food/Non-Feed Uses Considered in Registration Review 

Work Planning, November 8, 2010. 

Additional supporting documents for fipronil may be found in the registration review docket 

EPA-HQ-OPP-2011-0448 located on the internet at www.regulations.gov.
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I. Preliminary Work Plan – Fipronil 

Introduction:

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides sold or distributed in the United States generally must be registered by the 

Environmental Protection Agency (EPA), based on scientific data showing that they will not 

cause unreasonable risks to human health or the environment when used as directed on product 

labeling. The registration review program is intended to make sure that, as the ability to assess 

risk evolves and as policies and practices change, all registered pesticides continue to meet the 

statutory standard of no unreasonable adverse effects to human health or the environment. 

Changes in science, public policy, and pesticide use practices will occur over time. Through the 

registration review program, the Agency periodically reevaluates pesticides to make sure that as 

change occurs, products in the marketplace can be used safely. Information on this program is 

provided at: http://www.epa.gov/oppsrrd1/registration_review/.

The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. The Agency will consider benefits information and data as required by FIFRA. The 

public phase of registration review begins when the initial docket is opened for each case. The 

docket is the Agency’s opportunity to state what it knows about the pesticide and what additional 

risk analyses and data or information it believes are needed to make a registration review 

decision. After reviewing and responding to comments and data received in the docket during 

this initial comment period, the Agency will develop and commit to a final work plan and 

schedule for the registration review of fipronil. 

Fipronil is a non-systemic, chiral phenylpyrazole insecticide registered for use to control ants, 

beetles, cockroaches, fleas, mole crickets, ticks, termites, thrips, and other insects in a variety of 

agricultural and residential uses. It is formulated as a technical chemical, formulation 

intermediate, dust, granular, pelletted/tabletted, wettable powder, impregnated material, 

emulsifiable concentrate, flowable concentrate, soluble concentrate, solution-ready to use, or 

pressurized liquid, depending on the use. Fipronil degrades to form persistent and immobile 

degradates—fipronil sulfide (MB 45950), fipronil sulfone (MB 46136), and MB 46513. 

Current outdoor fipronil registered uses include broadcast treatment, in-furrow treatment, seed 

treatments, soil injection, and bait treatments. Fipronil also is registered for use by lawn care 

operators and pest control operators to treat areas such as golf courses and food handling 

establishments. Registered residential uses for fipronil include spot-on treatment for domestic 

animals and ant mound treatment. In addition, fipronil is registered for use on potatoes, turnips, 

and rutabagas. Fipronil was first registered in 1985; therefore, it was not subject to the 

reregistration requirements of FIFRA.
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Anticipated Risk Assessment and Data Needs:

The Agency anticipates requiring data for use in conducting a comprehensive ecological risk 

assessment, including an endangered species risk assessment, for all uses of fipronil. The 

Agency also anticipates requiring additional data for use in conducting human exposure risk 

assessments. Below is a summary of the issues relevant to the registration review of fipronil. 

Ecological Risk: 

• The most recent ecological risk assessment for fipronil was completed May 2007 in 

support of the registration for use on turnips and rutabagas. 

• The Agency has not conducted a risk assessment that supports a complete endangered 

species determination for fipronil. The ecological risk assessment planned during 

registration review will allow the Agency to determine whether fipronil’s use has “no 

effect” or “may affect” federally listed threatened or endangered species (listed species) 

or their designated critical habitats. When an assessment concludes that a pesticide’s use 

“may affect” a listed species or its designated critical habitat, the Agency will consult 

with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Service (the 

Services), as appropriate. 

• The Agency completed a recent endangered species risk assessment for the delta smelt 

(San Francisco Bay) in June 2010, and is currently in consultation with the U.S. Fish and 

Wildlife Service (USFWS) and/or the National Marine Fisheries Service (NMFS) (the 

Services). 

• On January 19, 2011, the Center for Biological Diversity and the Pesticide Action 

Network North America filed a lawsuit in the United States District Court for the 

Northern District of California, against the Environmental Protection Agency (EPA) for 

allegedly failing to undergo consultation with the United States Fish and Wildlife Service 

and the National Marine Fisheries Service regarding the effects of over 350 pesticides, 

including fipronil, on over 200 endangered and threatened species throughout the United 

States (Center for Biological Diversity, et al. v. EPA, et al., No. C 11-00293 (N.D.Cal.). 

• The Agency anticipates requiring the following data for fipronil and/or its degradates for 

use in conducting a complete ecological risk assessment, including an endangered species 

assessment: 

o Guideline 830.7840 - Water solubility (fipronil sulfide MB45950) 

o Guideline 835.2120 – Hydrolysis (fipronil sulfide MB45950, fipronil sulfone 

MB46136, and MB46513) 

o Guideline 835.2240 - Photodegradation in water (fipronil sulfide MB45950, 

fipronil sulfone MB46136, and MB46513) 

o Guideline 835.4100 - Aerobic soil metabolism (fipronil sulfide MB45950 and 

fipronil sulfone MB46136) 
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o Guideline 835.4300 - Aerobic aquatic metabolism (fipronil sulfide MB45950, 

fipronil sulfone MB46136, and MB46513) 

o Guideline 835.4400 - Anaerobic aquatic metabolism (fipronil sulfide MB45950, 

fipronil sulfone MB46136, and MB46513) 

o Guideline 835.6100 - Environmental chemistry analytical method - soil (fipronil, 

fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) 

o Guideline 835.6200 - Environmental chemistry analytical method - water 

(fipronil, fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) 

o Guideline 850.1010 - Freshwater invertebrate acute toxicity (MB46513) 

o Guideline 850.1025 - Oyster acute toxicity (fipronil sulfide MB45950, fipronil 

sulfone MB46136, and MB46513) 

o Guideline 850.1055 - Bivalve acute toxicity (fipronil sulfide MB45950, fipronil 

sulfone MB46136, and MB46513 

o Guideline 850.1075 - Freshwater fish acute toxicity (fipronil sulfide MB45950) 

o Guideline 850.1300 - Freshwater aquatic invertebrate life cycle (fipronil sulfide 

MB45950 and fipronil sulfone MB46136) 

o Guideline 850.1350 - Estuarine-marine invertebrate life cycle (fipronil and 

MB46513) 

o Guideline 850.1400 - Freshwater fish early life stage (fipronil sulfide MB45950, 

fipronil sulfone MB46136, and MB46513) 

o Guideline 850.1500 - Estuarine-marine fish early life stage/full life cycle (fipronil 

sulfide MB45950, fipronil sulfone MB46136, and MB46513) 

o Guideline 850.1730 - Bioaccumulation in fish (fipronil sulfide MB45950, fipronil 

sulfone MB46136, and MB46513) 

o Guideline 850.1735 - Whole sediment acute freshwater invertebrate toxicity 

(fipronil, fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) 

o Guideline 850.1740 - Whole sediment acute estuarine marine invertebrate toxicity 

(fipronil, fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) 

o Guideline 850.2100 - Avian oral (fipronil sulfide MB45950, fipronil sulfone 

MB46136, and MB46513) - bobwhite quail and house sparrow 

o Guideline 850.2300 - Avian reproduction (fipronil sulfide MB45950, fipronil 

sulfone MB46136, and MB46513) - bobwhite quail and mallard duck 

o Guideline 850.3020 - Honey bee acute contact (fipronil, fipronil sulfide 

MB45950, fipronil sulfone MB46136, and MB46513) 

o Guideline 850.3030 - Honey bee foliage residue toxicity (fipronil, fipronil sulfide 

MB45950, fipronil sulfone MB46136, and MB46513) 

o Guideline 850.3040 - Field testing for pollinators (fipronil) 

o Guideline 850.4100 - Seedling emergence Tier II (fipronil) 

o Guideline 850.4150 - Vegetative vigor Tier II (fipronil) 

o Guideline 850.4400/5400 - Aquatic plant Tier II (fipronil sulfide MB45950, 

fipronil sulfone MB46136, and MB46513) 

o Non-guideline: Hyalella azteca 42-d Test for Measuring the Effects of Sedimentassociated Contaminants on Survival, Growth, and Reproduction 

o Non-guideline: Life-cycle Test for Measuring the Effects of Sediment-associated 

Contaminants on Chironomus dilutus (formerly known as C. tentans) 
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o Non-guideline: Leptocheirus plumulosus (Chronic Toxicity of Marine and 

Estuarine Sediment-associated Contaminants) 

• Please refer to Registration Review– Preliminary Problem Formulation for Ecological 

Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for 

Fipronil, dated May 4, 2011, located in the docket, for a detailed discussion of these 

anticipated risk assessment and data needs.

Human Health Risk:

• The most recent human health risk assessment, including a drinking water assessment, for 

fipronil was completed in 2007 to support tolerances on imported rice. 

• The Agency anticipates requiring the following data for fipronil for use in conducting a 

complete human health risk assessment: 

o Guideline 860.1200 - Directions for Use 

o Guideline 860.1500 - Crop Field Trials (fipronil, fipronil sulfide MB45950, 

fipronil sulfone MB46136, and MB46513) – rice grain 

o Guideline 870.3250 - 90-Day Dermal Study (fipronil) 

o Guideline 870.3465 - 90-Day/28-Day Inhalation Study (fipronil) 

o Guideline 870.7800 – Immunotoxicity (fipronil) 

• After the additional toxicology studies that are expected to be required are submitted and 

reviewed, EPA will re-evaluate endpoints and safety/uncertainty factors for fipronil. 

• During registration review, the Agency anticipates revising the dietary risk assessment if 

the FQPA safety factor (SF) changes, if a new drinking water assessment reflects changes 

in the estimated drinking water concentration, or a request for a new use is received. 

• There are residential uses of fipronil. The residential exposure database is adequate to 

support the registration review process; however, an updated residential exposure 

assessment may be required under registration review based upon revisions to the 

Agency’s Residential Standard Operating Procedures (SOPs) which was reviewed by the 

Scientific Advisory Panel (SAP) in October 2009. Furthermore, if new data are 

identified which impact exposure estimates, or if new points of departure, a revised 

FQPA SF, or revisions to exposure policies and procedures are made, a new residential 

assessment will be conducted. An updated assessment of fipronil pet products will be 

conducted under registration review based upon the updates to the SOPs for Residential 

Exposure Assessment. 

• Residential bystander exposures might occur as a result of spray applications and off-site 

transport (e.g., spray drift or volatilization). Revisions to Agency policies and procedures 

may warrant the Agency to consider the need for a bystander inhalation risk assessment 

for fipronil during registration review. 
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• During registration review, the Agency may need to revise the aggregate assessment to 

include changes in the toxicological endpoints and uncertainty factors; this will be 

determined once additional toxicology studies that are required for all fipronil technical 

products as a condition of registration are submitted and reviewed by the Agency. 

• An updated occupational assessment and occupational post-application assessment may 

be required for any fipronil use scenario if new data are identified which impact exposure 

estimates, or if new points of departure, a revised FQPA SF, or revisions to exposure 

policies and procedures are made. 

• The Agency will modify tolerances as needed, and work to harmonize tolerance/MRLs 

where possible in key export markets during registration review. 

• For more information please refer to Fipronil: Human Health Assessment Scoping 

Document in Support of Registration Review, dated May 24, 2011, located in the docket.

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its most recent fipronil registration decision, EPA reviewed these 

data and selected the most sensitive endpoints for relevant risk assessment scenarios from the 

existing hazard database. However, as required by FFDCA section 408(p), fipronil is subject to 

the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 
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chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Fipronil is not 

among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for fipronil. For further information on 

the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test 

guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/. 

Timeline:

EPA has created the following estimated timeline for the completion of the fipronil registration 

review. 

Registration Review for Fipronil – Projected Registration Review Timeline

Activities Estimated Date 

Opening the Docket 

Open Docket and Public Comment Period 2011 – June 

Close Public Comment 2011 – August 

Case Development 

Final Work Plan 2011 – November 

Issue DCI 2012 – July – September 

Data Submission 2014 – July – September 

Open Public Comment Period for Draft Risk Assessments 2015 – Jan. – March 

Close Public Comment Period 2016 – April – June 

Registration Review Decision 

Open Public Comment Period for Proposed Registration Review 

Decision 

 2016 – July – September 

Close Public Comment Period 2016 – October – 

December 

Registration Review Decision and Begin Post-Decision Follow-up 2017 

Total (years) 6 

Guidance for Commenters:

The public is invited to comment on EPA’s preliminary work plan and rationale. The Agency 

will carefully consider all comments as well as any additional information or data provided in a 

timely manner prior to issuing a Final Work Plan for fipronil. 

Trade Irritants:

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. Growers and 

other stakeholders are asked to comment on any trade irritant issues resulting from lack of MRLs 

or disparities between U.S. tolerances and MRLs in key export markets, providing as much 

specificity as possible regarding the nature of the concern. 
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Water Quality:

Total Maximum Daily Loads (TMDL) have been developed for fipronil in six water bodies that 

were listed as impaired under section 303(d) of the Clean Water Act in Louisiana1 2

. More 

information on impaired water bodies and TMDLs can be found at the Agency’s website3

. The 

Agency invites submission of water quality data for this pesticide. To the extent possible, data 

should conform to the quality standards in Appendix A of the OPP Standard Operating 

Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s 

Registration Review Risk Assessment and Management Process4

 in order to ensure they can be 

used quantitatively or qualitatively in pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to fipronil, compared to the general population. Please 

comment if you are aware of any sub-populations that may have atypical, unusually high 

exposure compared to the general population. 

Additional Information:

Stakeholders are also specifically asked to provide information and data that will assist the 

Agency in refining its risk assessments, including any species-specific ecological effects 

determinations. The Agency is interested in receiving the following information: 

1. confirmation on the following label information 

a. sites of application 

b. formulations 

c. application methods and equipment 

d. maximum application rates in units related to mass per unit area of treatment 

zone 

e. frequency of application, application intervals and maximum number of 

applications per season 

f. geographic limitations on use 

2. use or potential use distribution (e.g., acreage and geographical distribution of 

relevant crops) 

3. use history 

4. median and 90th percentile reported use rates (lbs. a.i./acre) from usage data – 

national, state, and county 

5. application timing (date of first application and application intervals) by crop – 

national, state and county 

 

1 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885 2 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_group_name=PESTICIDES 3 http://www.epa.gov/owow/tmdl/

4 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
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6. sub-county crop location data 

7. directly acquired county-level usage data (not derived from state level data) 

a. maximum reported use rate (lbs. a.i./acre) from usage data – county 

b. percent crop treated – county 

c. median and 90th percentile number of applications – county 

d. total pounds per year – county 

e. the year the pesticide was last used in the county/sub-county area 

f. the years in which the pesticide was applied in the county/sub-county area 

8. typical interval (days) 

9. state or local use restrictions 

10. ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian 

and mammalian mortalities) not already reported to the Agency 

11. monitoring data 

12. information on why use shows up on potatoes for the first time in 2008 

Next Steps:

After the 60-day comment period closes, the Agency will review and respond to any comments 

received in a timely manner, and expects to issue a Final Work Plan for fipronil during 

November, 2011. 
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II. FACT SHEET 

Background Information:

• Fipronil registration review case number 7423 

• Fipronil PC code: 129121 

• The first fipronil-containing pesticide was registered in the U.S. in 1985; therefore, it was 

not subject to the reregistration process under FIFRA. 

• There are currently 85 FIFRA Section 3 registrations and 7 Section 24(c) registrations for 

fipronil.

• Technical registrants for fipronil include: Bayer Environmental Science, BASF 

Corporation, Irvita Plant Protection N.V., Argite, LLC, Fipronex Solutions, Inc., and 

Raymat Materials, Inc.

• Tolerances for residues of fipronil exist under 40 CFR §180.517. 

• Pesticide Re-evaluation Division (PRD) Chemical Review Manager (CRM): Susan 

Bartow, bartow.susan@epa.gov

• Registration Division (RD) Product Manager (PM): Richard Gebken, 

gebken.richard@epa.gov

Use & Usage Information: For additional details, please refer to Appendix A: Food/Feed & 

Non-Food/Non-Feed Uses Considered in Registration Review Work Planning, November 8, 

2010; Screening Level Usage Analysis (SLUA), August 24, 2010; and BEAD Chemical Profile 

for Registration Review: Fipronil (PC Code: 129121 May 25, 2011).

• Fipronil is a non-systemic, chiral phenylpyrazole insecticide registered for use to control 

ants, beetles, cockroaches, fleas, mole crickets, ticks, termites, thrips, and other insects. 

Fipronil is registered for outdoor use, in-furrow treatment, seed treatment, soil injection, 

and bait treatments. In terms of non-agricultural usage, fipronil is registered for use by 

lawn care operators and pest control operators to treat golf courses and food handling 

establishments. Fipronil is registered for use on potatoes, turnips, and rutabagas. 

• There are residential uses for fipronil. It is registered for use for spot-on treatment on 

domestic animals and ant mound treatment at residential settings. 

• Fipronil is formulated as dust, granules, pelleted/tableted, wettable powder, impregnated 

material, water dispersible granules, emulsifiable concentrate, flowable concentrate, 

soluble concentrate or soluble ready-to-use. End-use product concentrations range from 

0.0001 – 80 percent active ingredient. 

• Application methods include spot treatment, crack and crevice treatment, bait application, 

broadcast, mound treatment, subsurface/slit application treatment, animal treatments 

(rub-on and spray methods), and soil/media treatment. Application equipment includes 

low pressure ground sprayer, ready-to-use spray container, foam-making generator, 

airplane, and helicopter.
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Recent Actions:

• Tolerances for residues of fipronil, including its metabolites and degradates, in or on 

turnip and rutabaga were extended until December 31, 2013 (FR Vol. 75 No. 245, 

December 22, 2010). EPA has authorized under FIFRA section 18 the use of fipronil on 

turnip and rutabaga for control of cabbage maggot in Oregon. This regulation extends 

time-limited tolerances for combined residues of fipronil for an additional 3-year period. 

• A Federal Register notice for fipronil was issued on February 3, 2010 (FR Vol. 75 No. 

22) which announced the expiration of certain corn-in-furrow and turfgrass end-use 

fipronil products registered under section 3 of FIFRA. The notice also announced the 

amendment to terminate uses of all corn-in-furrow end use fipronil products registered 

under section 3 of FIFRA, and included a cancellation order to provide for existing stocks 

of affected products. 

• In 2009, conditional registrations of outdoor granular turf products were converted to 

unconditional registrations and the use status was changed to Restricted Use Pesticide 

(RUP). All non-RUP granular products labeled for turf and residential landscapes, and 

that would be applied over wide areas were cancelled. All remaining corn uses were also 

cancelled except for corn seed treatments on seed intended for export only. 

Ecological Risk Assessment Status: 

The following are key findings of the most recent ecological risk assessments for fipronil. Please 

refer to Registration Review– Preliminary Problem Formulation for the Ecological Risk and 

Environmental Fate, Endangered Species, and Drinking Water Assessments for Fipronil May 4, 

2011, located in the docket, for a detailed discussion of the ecological risk assessments. 

• The most recent ecological risk assessment of fipronil was completed in May 2007 in 

support of the registration for use to control Cabbage Maggot on turnips and rutabagas.

• The Agency has conducted more than 20 ecological risk assessments for fipronil. These 

assessments have identified the following risk concerns:

o Acute and chronic risks to freshwater, estuarine, and marine invertebrates

o Acute risk to endangered freshwater invertebrates 

o Direct chronic risks to both fresh- and saltwater fish species 

o Indirect effects to endangered fish species 

o Acute lethal and reproduction risks to birds 

o Reproductive effects in insectivorous mammals 

o Acute and chronic terrestrial vertebrate risk 
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• To mitigate ecological risks, the major remaining outdoor use products were converted to 

restricted use classification, to avoid indiscriminate use by homeowners. Additionally, 

the Agency recommended setbacks for applications near bodies of water (buffer zones), 

and prohibition of applications near outdoor drainage areas, storm drains, french drains, 

etc. Additional mitigation included cancellation of the corn-in furrow use, and corn seed 

treatment use (except for corn seed treatments on seed intended for export only). 

Human Health Risk Assessment Status:

The following are key findings of the most recent human health risk assessments for fipronil. 

Please refer to Fipronil: Human Health Assessment Scoping Document in Support of 

Registration Review, dated May 24, 2011, located in the docket, for a detailed discussion of the 

human health risk assessment. 

The most recent human health risk assessment for fipronil was completed in 2007 to support the 

tolerance on imported rice. 

Hazard Characterization: 

• Fipronil has moderate acute toxicity (Category II) by the oral and inhalation routes in 

rats. By the dermal route, it is of moderate toxicity in rabbits, and low toxicity (Category 

III) in rats. Fipronil technical is relatively non-irritating to the skin (Category IV) and 

eye (Category III) of rabbits and is not a dermal sensitizer. 

• The Agency reduced the 10x FQPA Safety Factor to 1x because of the overall quality of 

the database, the low degree of concern for susceptibility, and the lack of evidence of 

neurotoxicity. 

• The carcinogenic potential of fipronil has been classified as a Group C, possible human 

carcinogen, based on increases in thyroid follicular cell tumors in both sexes of the rat, 

which were statistically significant by both pair-wise and trend analyses. There is no 

apparent concern for mutagenicity (no mutagenic activity). In 1998, the Agency’s 

Hazard Identification Assessment Review Committee (HIARC) determined that dietary 

risk concerns from the long-term consumption of fipronil residues could be adequately 

addressed in chronic dietary exposure analyses using the RfD. Therefore, a separate 

assessment of cancer risk was deemed unnecessary. A cancer aggregate risk assessment 

was not performed because HIARC determined that cancer dietary risk concerns due to 

long-term consumption of fipronil residues are adequately addressed by the chronic 

exposure assessment. 
15

Dietary: 

• Acute and refined chronic dietary risk analyses were conducted using the DEEM-FCIDTM 

model to estimate the exposure to fipronil. The acute and refined chronic risk estimates 

were below the level of concern for each population subgroup. 

Residential: 

• An assessment in 2000 evaluated homeowner exposure from the registered fipronil 

products used to control fire ants. Margins of exposure (MOE) for dermal contact and 

inhalation resulting from assessment of granular formulations were not of concern. 

• Assessments of the application of fipronil pet shampoo, spot-on and spray-on products 

did not identify any risks of concern. 

• Adult dermal and child (3 to < 6 years old) dermal and incidental oral post-application 

exposure (combined) were previously assessed and these were not of concern to the 

Agency. 

Aggregate: 

• Based on fipronil’s existing uses, the worst case aggregate exposure for adults is 

represented by their combined estimated handler dermal and inhalation exposures 

resulting from applying a fipronil product to control fire ants. The worst case aggregate 

exposure for children younger than 6 years old is represented by their combined 

estimated post-application dermal and incidental oral exposures resulting from contact 

with fipronil-treated pets. These combined exposures/risks along with average food and 

drinking water exposure estimates were used to determine short- and intermediate 

aggregate risks. These aggregate risk estimates were below the Agency's level of concern 

for children and adults. 

Occupational: 

• Results from assessments of occupational handler scenarios previously evaluated indicate 

that short- and intermediate-term exposure/risks were not of concern to the Agency at 

either baseline or minimum level of personal protection.

• Occupational post-application exposure to fipronil is anticipated to occur based on the 

following use patterns of the chemical—in-furrow, seed treatment, pet treatment, and 

broadcast on turf. Dermal post-application occupational exposure based on the in-furrow 

uses of fipronil are expected to be negligible as the soil is normally not contacted after 

incorporation. The seed treatment use is for field corn seed to be exported only, and 

secondary handlers are not involved; therefore post-application exposure to fipronil 

treated seeds is not expected to occur. Domestic pets are expected to be treated and 

immediately returned to their owners such that post-application contact will be negligible 
16

and an occupational post-application dermal exposure assessment was not performed for 

this use. For the broadcast turf use, post-application exposure also is expected to be 

negligible. 

Human Studies: 

• Past fipronil risk assessments rely in part on data from studies in which adult human 

subjects were intentionally exposed to a pesticide to determine their dermal and 

inhalation exposure. Many such studies, involving exposure to many different pesticides, 

comprise generic pesticide exposure databases such as PHED, the Outdoor Residential 

Exposure Task Force (ORETF) Database, and the Agricultural Reentry Task Force 

(ARTF) Database. EPA has reviewed all the studies supporting these multi-pesticide 

generic exposure databases, and has found no clear and convincing evidence that the 

conduct of any of them was either fundamentally unethical or significantly deficient 

relative to the ethical standards prevailing at the time the research was conducted. All 

applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research 

(40 CFR Part 26) have been satisfied, and there is no regulatory barrier to continued 

reliance on these studies. 

Cumulative: 

• The Agency has not determined whether fipronil shares a common mechanism of toxicity 

with other chemical substances. If, in the future, the Agency determines that new 

information on fipronil is available that could potentially impact a cumulative risk 

assessment, the Agency will revisit the need for one.

Incidents:

• The Office of Pesticide Programs (OPP) Incident Data System (IDS) was consulted for 

reports of fipronil incidents. From 2002 to 2010, 4,243 incidents involving fipronil were 

reported. Although the frequency of incidents appears to be decreasing over time and the 

majority of incidents were low to moderate severity, there were eight incidents classified 

as having major severity and one incident resulted in a death due to an allergic reaction. 

Based on the number of incidents reported involving fipronil, and the effects noted in the 

incidents, the evaluation warrants further analysis in the preliminary risk assessment 

phase of registration review. This further analysis will include reviewing other incident 

data from other sources (such as, Sentinel Event Notification System for Occupational 

Risks (SENSOR) and Poison Control Center (PCC)) as well as the National Institute for 

Occupational Safety and Health (NIOSH) article Acute illnesses associated with exposure 

to fipronil—surveillance data from 11 states in the United States, 2001–2007 (Lee, et al. 

2010. Clin Toxicol 2010; 48:737-44). 

• There are 49 incidents in the Agency database for effects on non-target organisms 

associated with the labeled use of fipronil in the United States. The reported incidents 

involved crawfish and corn crops. The likelihood of fipronil as the cause of the incidents 
17

was classified as highly probable for one incident, probable for one incident, and possible 

for one incident. Two additional incidents were reported outside the United States—one 

incident involved bird species and termites, but did not contain confirmatory analytical 

data, and the other incident involved honeybee hive mortality, but the findings are 

uncertain because another pesticide besides fipronil was also implicated in the honeybee 

hive incident.

• Several pet incidents have been reported to the Agency. The Agency is developing 

mitigation measures to address these incidents. Please see the Agency’s website 

(http://www.epa.gov/pesticides/health/spot-on-meetings.html) for more information.

Tolerances and International Harmonization:

• Tolerances are established for residues of fipronil under 40 CFR §180.517. Currently, 

the 40 CFR § 180.517 has permanent tolerances for fipronil (which include its 2 

metabolites and 1 photodegradate) in/on: field corn grain, stover and forage; the fat, liver, 

meat and meat byproducts (except liver) of cattle, goat, hog, horse and sheep; eggs; milk 

fat; potato and potato wet peel; poultry fat, meat and meat byproducts; and rice grain and 

straw. Time-limited tolerances for turnip and rutabaga are in effect until December 31, 

2013. Finally, tolerances for indirect or inadvertent residues are established in/on wheat, 

grain, forage, hay, and straw.

• Compliance with the tolerance levels specified below is to be determined by measuring 

fipronil (5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(1R,S) (trifluoromethyl) 

sulfinyl]-1H-pyrazole-3-carbonitrile) and its metabolites 5-amino-1-[2,6-dichloro-4-

(trifluoromethyl) phenyl]-4-[(trifluoromethyl) sulfonyl]-1H-pyrazole-3-carbonitrile and 

5-amino-1-[2,6-dichloro-4-(trifluoromethyl) phenyl]-4-[(trifluoromethyl)thio]-1Hpyrazole-3-carbonitrile and its photodegradate 5-amino-1-(2,6-dichloro-4-

(trifluoromethyl)phenyl]-4-[(1R,S)-(trifluoromethyl)]-1H-pyrazole-3-carbonitrile.

• A Codex MRL has been established for fipronil residues in several raw agricultural 

commodities. The proposed import tolerance is not harmonized with the established 

MRL, a fact attributable to the difference in tolerance expression between Codex and the 

U.S. There are currently no established Canadian and Mexican MRLs for fipronil.

• The Agency plans to revoke the tolerance for rice straw and potato wet peel in 40 CFR § 

180.517. A tolerance of 0.10 ppm for processed potato waste should be included. The 

Agency also plans to modify the tolerance expression in the 40 CFR § 180.517 according 

to the new Interim Guidance on Tolerance Expressions. 

• The Agency has required data from Japan and crop field trials from Brazil to support a 

previous petition for imported rice uses and several fipronil label amendments. For the 

Japanese trials, information concerning the field portion of the study and the analytical 

portion of the study must be submitted. To support the proposed foliar use in Brazil, data 

are required which depict magnitude of the residues of fipronil and its metabolites MB 
18

45950, MB 46136, and MB 46513 in/on rice grain harvested 30 days following 

postemergence foliar treatment of the proposed formulated product at 12 g ai/ha. 

• The Agency has required additional information pertaining to typical application patterns 

in the countries of use. The submitted use directions information for Australia does not 

include information on formulation type and a.i. percentages/product density so that 

applications rates could be converted from product to active ingredient. The submitted 

use information for Brazil (spray application) does not include maximum number of 

applications per season and/or maximum seasonal rate. In addition, the Agency has 

required that the petitioner provide assurance that the only countries in which their 

fipronil products will be used on rice destined for import into the U.S. are Australia, 

Brazil, and Japan. 

Data Call-In Status

• No data call-ins have been issued for fipronil. 

Labels: 

• Fipronil Section 3 product labels can be obtained from the Pesticide Product Label 

System (PPLS) website: http://oaspub.epa.gov/pestlabl/ppls.hom. 
19

III. Summary of Data Gaps – Fipronil 

The table below summarizes all anticipated data needs for fipronil in Section I, of this 

document (Preliminary Work Plan), the Registration Review– Preliminary Problem 

Formulation for the Ecological Risk and Environmental Fate, Endangered Species, and 

Drinking Water Assessments for Fipronil, dated May 4, 2011, and the Fipronil: Human 

Health Assessment Scoping Document in Support of Registration Review, dated May 24, 

2011. 

Guideline 

Number Anticipated Data Requirement Test Material 

Study 

Duration 

(months) 

830.7840 Water Solubility (fipronil sulfide MB45950) TGAI 12 

835.2120 Hydrolysis(fipronil sulfide MB45950, fipronil 

sulfone MB46136,and MB46513) TGAI 12 

835.2240 

Photodegradation in water (fipronil sulfide 

MB45950, fipronil sulfone MB46136, and 

MB46513) 

TGAI 12 

835.4100 Aerobic soil metabolism (fipronil sulfide MB45950 

and fipronil sulfone MB46136) TGAI 24 

835.4300 

Aerobic Aquatic Metabolism (fipronil sulfide 

MB45950, fipronil sulfone MB46136, and 

MB46513) 

TGAI 24 

835.4400 

Anaerobic Aquatic Metabolism (fipronil sulfide 

MB45950, fipronil sulfone MB46136, and 

MB46513) 

TGAI 24 

835.6100 

Environmental chemistry analytical method - soil 

(fipronil, fipronil sulfide MB45950, fipronil sulfone 

MB46136, and MB46513) 

TEP 24 

835.6200 

Environmental chemistry analytical method - water 

(fipronil, fipronil sulfide MB45950, fipronil sulfone 

MB46136, and MB46513) 

TEP 24 

850.1010 Freshwater invertebrate acute toxicity (MB46513) TGAI 24 

850.1025 Oyster acute toxicity (fipronil sulfide MB45950, 

fipronil sulfone MB46136, and MB46513)1 TGAI 12 

850.1055 Bivalve acute toxicity (fipronil sulfide MB45950, 

fipronil sulfone MB46136, and MB46513)1 TGAI 12 

850.1075 Freshwater fish acute toxicity (fipronil sulfide 

MB45950) TGAI 18 

850.1300 Freshwater aquatic invertebrate life cycle (fipronil 

sulfide MB45950 and fipronil sulfone MB46136) TGAI 12 

850.1350 Estuarine-marine invertebrate life cycle (fipronil 

and MB46513) TGAI 12 

850.1400 Freshwater fish early life stage (fipronil sulfide 

MB45950, fipronil sulfone MB46136, and TGAI 12 
20

Guideline 

Number Anticipated Data Requirement Test Material 

Study 

Duration 

(months) 

MB46513) 

850.1500 

Estuarine-marine fish early life stage/full life cycle 

(fipronil sulfide MB45950, fipronil sulfone 

MB46136, and MB46513) 

TGAI 24 

850.1730 Bioaccumulation in Fish (fipronil sulfide MB45950, 

fipronil sulfone MB46136, and MB46513) TGAI 12 

850.1735 

Whole sediment acute freshwater invertebrate 

toxicity (fipronil, fipronil sulfide MB45950, fipronil 

sulfone MB46136, and MB46513) 

TGAI 24 

850.1740 

Whole sediment acute estuarine marine invertebrate 

toxicity (fipronil, fipronil sulfide MB45950, fipronil 

sulfone MB46136, and MB46513) 

TGAI 12 

850.2100 

Avian oral (fipronil sulfide MB45950, fipronil 

sulfone MB46136, and MB46513) - bobwhite quail 

and house sparrow 

TGAI 12 

850.2300 

Avian reproduction (fipronil sulfide MB45950 and 

fipronil sulfone MB46136, and MB46513) - 

bobwhite quail and mallard duck 

TGAI 24 

850.3020 

Honey bee acute contact (fipronil, fipronil sulfide 

MB45950, fipronil sulfone MB46136, and 

MB46513) 

TEP 12 

850.3030 

Honey bee foliage residue toxicity (fipronil, fipronil 

sulfide MB45950, fipronil sulfone MB46136, and 

MB46513) 

TEP 12 

850.3040 Field testing for pollinators (fipronil) TEP 24 

850.4100 Seedling emergence Tier II (fipronil)2 TEP 12 

850.4150 Vegetative vigor Tier II (fipronil)2 TEP 12 

850.4400 Aquatic plant tier II (fipronil sulfide MB45950, 

fipronil sulfone MB46136, and MB46513)2 TEP 12 

850.5400 Aquatic plant tier II (fipronil sulfide MB45950, 

fipronil sulfone MB46136, and MB46513)2 TEP 12 

860.1200 Directions for Use TEP 12 

860.1500 

Crop Field Trials (fipronil, fipronil sulfide 

MB45950, fipronil sulfone MB46136, and 

MB46513) – rice grain 

TEP 24 

870.3200 90-Day Dermal Study (fipronil) TGAI 24 

870.3465 90-Day Inhalation Toxicity3 (fipronil) TGAI 24 

870.7800 Immunotoxicity (fipronil) TGAI 12 

Non-guideline 

Hyalella azteca 42-d Test for Measuring the Effects 

of Sediment-associated Contaminants on Survival, 

Growth, and Reproduction4

TGAI 24

Non-guideline 

Life-cycle Test for Measuring the Effects of 

Sediment-associated Contaminants on Chironomus 

dilutus (formerly known as C. tentans)5

TGAI 24
21

Guideline 

Number Anticipated Data Requirement Test Material 

Study 

Duration 

(months) 

Non-guideline 

Leptocheirus plumulosus (Chronic Toxicity of 

Marine and Estuarine Sediment-associated 

Contaminants)6

TGAI 24

1

 The anticipated DCI is expected to provide that registrants may conduct either Guideline 850.1025 

(Oyster acute toxicity) or Guideline 850.1055 (Bivalve acute toxicity) although they should be the same 

across all chemicals and should match for parent (Crassostrea virginianus was tested using fipronil). 2

 A Tier II study is required. A Tier I plant study may be conducted in lieu of a Tier II study with the 

understanding that any adverse effects observed by the Tier I study would necessitate conduct and 

submission of a Tier II study as well. 

3

 Based on expected duration of exposure, the anticipated DCI is expected to provide that registrants 

may conduct a 28-Day inhalation toxicity study in lieu of a 90-day study. 

4 Registrants must use the test method: Hyalella azteca 42-day Test for Measuring the Effects of 

Sediment-associated Contaminants on Survival, Growth, and Reproduction. In USEPA 2000. Methods 

for Measuring the Toxicity and Bioaccumulation of Sediment-associated Contaminants with 

Freshwater Invertebrates. EPA 600/R-99/064. 5 Registrants must use the test method: Life-cycle Test for Measuring the Effects of Sedimentassociated Contaminants on Chironomus dilutus (formerly known as C. tentans). In USEPA 2000. 

Methods for Measuring the Toxicity and Bioaccumulation of Sediment-associated Contaminants with 

Freshwater Invertebrates. EPA 600/R-99/064. 6 Registrants must use the test method: Leptocheirus plumulosus. In USEPA 2001. Method for 

Assessing the Chronic Toxicity of Marine and Estuarine Sediment-associated Contaminants with the 

Amphipod Leptocheirus plumulosus. EPA 600/R-0l/020.